8zb0
Cryo-EM structure of human ZnT1
Structural highlights
FunctionZNT1_HUMAN Zinc ion:proton antiporter that could function at the plasma membrane mediating zinc efflux from cells against its electrochemical gradient protecting them from intracellular zinc accumulation and toxicity (PubMed:31471319). Alternatively, could prevent the transport to the plasma membrane of CACNB2, the L-type calcium channels regulatory subunit, through a yet to be defined mechanism. By modulating the expression of these channels at the plasma membrane, could prevent calcium and zinc influx into cells. By the same mechanism, could also prevent L-type calcium channels-mediated heavy metal influx into cells (By similarity). In some cells, could also function as a zinc ion:proton antiporter mediating zinc entry into the lumen of cytoplasmic vesicles. In macrophages, can increase zinc ions concentration into the lumen of cytoplasmic vesicles containing engulfed bacteria and could help inactivate them (PubMed:32441444).[UniProtKB:Q62720][1] [2] Publication Abstract from PubMedThe essential trace element, zinc, regulates virtually all aspects of cellular physiology, particularly cell proliferation and survival. Diverse families of metal transporters, metallothioneins, and metal-responsive transcriptional regulators are linked to zinc homeostasis. However, the mechanism underlying the regulation of systemic zinc homeostasis remains largely unknown. Here, it is reported that the intestinal transporter SLC30A1 plays an essential role in maintaining systemic zinc homeostasis. Using several lines of tissue-specific knockout mice, it is found that intestinal Slc30a1 plays a critical role in survival. Furthermore, lineage tracing reveals that Slc30a1 is localized to the basolateral membrane of intestinal epithelial cells (IECs). It is also found that Slc30a1 safeguards both intestinal barrier integrity and systemic zinc homeostasis. Finally, an integrative analysis of the cryo-EM structure and site-specific mutagenesis of human SLC30A1 are performed and a zinc transport mechanism of SLC30A1 unique within the SLC30A family, with His43 serving as a critical residue for zinc selectivity, is identified. The Intestinal Transporter SLC30A1 Plays a Critical Role in Regulating Systemic Zinc Homeostasis.,Sun S, Xie E, Xu S, Ji S, Wang S, Shen J, Wang R, Shen X, Su Y, Song Z, Wu X, Zhou J, Cai Z, Li X, Zhang Y, Min J, Wang F Adv Sci (Weinh). 2024 Dec;11(46):e2406421. doi: 10.1002/advs.202406421. Epub 2024 , Oct 18. PMID:39422023[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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